METHYLMERCURY-INDUCED ASTROCYTIC SWELLING IS ASSOCIATED WITH ACTIVATION OF THE NA+ H+ ANTIPORTER, AND IS FULLY REVERSED BY AMILORIDE/

Astrocytes are a known 'sink' for brain methylmercury (MeHg) depositio n. Yet, the significance of the preferential accumulation of MeHg with in these cells is imprecisely defined. To determine whether MeHg in is otonic buffer has the potential to interfere with homeostatic function s, we measured its effect on astrocytic Volume using an electrical imp edance method [E.R. O'Connor, H.K. Kimelbeg, C.R. Keese, I. Giaever, E lectrical impedance method for measuring volume changes in astrocytes, Am. J. Physiol. 264 (1993) C471-C478.]. In addition, we have characte rized the alterations in astrocytic ion permeability associated with e xposure to this organometal. The results show that MeHg rapidly induce s astrocytic swelling, and that this effect is secondary to increased astrocytic Na+ uptake. Furthermore, the effect of MeHg on astrocytic s welling is completely inhibited by amiloride, but not by SITS cetamido -4'-isothiocyanatostilbene-2,2'-disulfonic acid), furosemide, or bumet anide. Accordingly, increased cellular permeability to Na+ via the Na/H+ antiporter is invoked as the primary mechanism of MeHg-induced ast rocytic swelling. (C) 1998 Elsevier Science B.V. All rights reserved.